Disease in the Cervical Spine Fusion in the Treatment of Symptomatic Degenerative Disc Mobi-C Cervical Artificial Disc to Anterior Discectomy and Investigational Device Exemption Clinical Trial Comparing Multi-center , Prospective , Randomized , Controlled

Background Anterior cervical discectomy and fusion (ACDF) is the gold standard for treating symptomatic cervical disc degeneration. Cervical total disc replacements (TDRs) have emerged as an alternative for some patients. The purpose of this study was to evaluate the safety and effectiveness of a new TDR device compared with ACDF for treating singlelevel cervical disc degeneration. Methods This was a prospective, randomized, controlled, multicenter Food and Drug Administration (FDA) regulated Investigational Device Exemption (IDE) study. A total of 245 patients were treated (164 TDR: 81 ACDF). The primary outcome measure was overall success based on improvement in Neck Disability Index (NDI), no subsequent surgical interventions, and no adverse events (AEs) classified as major complications. by guest on May 22, 2019 http://ijssurgery.com/ Downloaded from Secondary outcome measures included SF-12, visual analog scale (VAS) assessing neck and arm pain, patient satisfaction, radiographic range of motion, and adjacent level degeneration. Patients were evaluated preoperatively and postoperatively at 6 weeks, 3, 6, 12, 18, and 24 months. The hypothesis was that the TDR success rate was non-inferior to ACDF at 24 months. Results Overall success rates were 73.6% for TDR and 65.3% for ACDF, confirming noninferiority (p < 0.0025). TDR demonstrated earlier improvements with significant differences in NDI scores at 6 weeks and 3 months, and VAS neck pain and SF-12 PCS scores at 6 weeks (p<0.05). Operative level range of motion in the TDR group was maintained throughout follow-up. Radiographic evidence of inferior adjacent segment degeneration was significantly greater with ACDF at 12 and 24 months (p < 0.05). AE rates were similar. Conclusions Mobi-C TDR is a safe and effective treatment for single-level disc degeneration, producing outcomes similar to ACDF with less adjacent segment degeneration. Level of Evidence: Level I. Clinical relevance: This study adds to the literature supporting cervical TDR as a viable option to ACDF in appropriately selected patients with disc degeneration. keywords: clinical outcome, randomized study, anterior cervical fusion, Cervical Spine, total disc replacement Volume 8 Article 7 doi: 10.14444/1007 Introduction Cervical disc degeneration is known to be a primary cause of neck pain and neurologic symptoms and can cause significant morbidity.1 Degeneration can be related to radiculopathy or myelopathy due to compression of spinal nerves and/or spinal cord.2 Decompressive surgery has been shown to be effective at reducing symptoms. Anterior cervical discectomy and fusion (ACDF) has been established as the primary surgical technique to decompress the spinal cord and nerve roots.3 There are three main goals of ACDF: decompression of the neural element, maintenance of lordosis, and stabilization of the motion segment.4 Typically, bone graft or a cage in conjunction with a rigid anterior plate are implanted to maintain or restore disc space integrity, provide stability, and facilitate fusion. With ACDF good clinical outcomes are generally achieved in a high percentage of patients.5, 6, 7 In particular, procedures which use allograft bone and an anterior plate produce overall positive patient outcomes, reduce post-operative bracing, and reduce complications associated with graft resorption, migration, and subsidence.8 Long term reduction in symptoms associated with degenerative disc disease (DDD) has led to ACDF being generally accepted as the gold standard of treatment for indicated patients.9 Despite benefits of ACDF, it is not without complications. ACDF with allograft bone and anterior plating has been associated with complications such as screw back out, plate fracture, dysphagia, adjacent segment degeneration, and pseudoarthrosis.6,10,11 by guest on May 22, 2019 http://ijssurgery.com/ Downloaded from Artificial cervical discs have been used since the 1990’s.12, 13 Total disc replacement (TDR), as an alternative to ACDF in the treatment of symptomatic cervical DDD, is becoming increasingly common and potentially provides some advantages over ACDF. Not only does TDR provide the same anterior neural decompression and maintenance of disc space as ACDF14, it can also preserve segmental mobility.15 Recently several Food and Drug Administration (FDA) Investigational Device Exemption (IDE) trials have demonstrated that TDR is at least as safe and effective as ACDF for of single-level symptomatic cervical DDD.16, 17, 18 Furthermore, these studies found that TDR preserves segmental mobility and these patients tended to have better clinical outcomes earlier after surgery and maintained good quality clinical outcomes at 2 years postoperatively. Additionally, longer term studies found that TDR provides excellent clinical outcomes 5 to 8 years post-operatively.19, 20, 21 Good clinical outcomes for cervical TDRs have also been demonstrated in European studies.22, 23 One potential advantages of TDR over fusion was the reduction of adjacent segment degeneration (ASD). Reports on the clinical impact of ASD have been mixed, with some variation attributable to there being radiographic findings of ASD not associated with clinical symptoms. Nunley et al. reported a rate of ASD in TDR patients of 3.1% per year.24 Although not a primary part of their study, comparison to ACDF found no significant difference in the occurrence rate. Other studies have found an increased rate of ASD in fusion patients based on either radiographic findings25 or a trend toward a higher rate of re-operation at the adjacent segment to treat new symptoms.26 The Mobi-C Artificial Cervical Disc (LDR Medical; Troyes, France) was introduced outside the United States in November 2004. A European non-comparative, prospective, multi-center study evaluated the safety and efficacy of this device in the treatment of cervical DDD in 335 patients. This study found statistically significant improvements in clinical outcomes and pain scores compared to baseline at 24 months post-operatively.22, 23 The current study reports the 2-year follow-up results of a prospective, randomized, concurrently controlled, multicenter clinical trial to determine the safety and efficacy of TDR with the Mobi-C Artificial Cervical Disc versus ACDF at a single level for treatment of symptomatic cervical DDD. The hypothesis was that clinical outcomes of patients treated with TDR would not be inferior to outcomes of patients with the control treatment at 24 months. Material and Methods Study design A non-inferiority study design with a 2:1 randomization (TDR: control) was prospectively planned for this FDA-regulated IDE study. A 5% advantage was hypothesized based on pilot study data. A projected 75% success rate for control and 80% success rate for TDR with respect to the primary endpoint was used along with the 2:1 randomization scheme. A total sample size of 222 randomized cases (148 TDR vs. 74 control) was determined to meet statistical power requirements to test for non-inferiority with the one-sided 95% lower confidence bound on the difference exceeding -10%. An additional 10% was added by guest on May 22, 2019 http://ijssurgery.com/ Downloaded from to the 222 to account for patients that may be lost to follow-up, bringing the total sample size to 245. The population discussed in this report, with the exception of peri-operative data and adverse events, is the Intent-To-Treat population (ITT), which consisted of all subjects who were randomized and received study surgery. The ITT population consisted of 164 TDR patients and 81 control patients. Peri-operative data is presented for the Safety Population, which included all patients in the ITT population as well as the 15 nonrandomized training cases. All principle investigators were trained on the surgical technique for the study device as part of this IDE; which did consist of a separate two-level arm ran concurrently and using the same investigational device.27 Each site was allotted one training case with the investigational device; 15 sites performed training cases for a one level indication, all others performed training with a two level case. This resulted in 15 additional TDR patients (the non-randomized training cases) in the one level IDE. The primary endpoint of the investigation was a composite measure assessed at 24 months. To be considered a success a patient had to be successful in each of the following three measures: 1) NDI success, a 30 point improvement in score if baseline NDI score was greater than or equal to 60, or a 50% of baseline score improvement in NDI score if baseline NDI scores were less than 60, 2) No device related subsequent surgical intervention at the index level (defined as removal, revision, supplemental fixation, or reoperation), and 3) No study defined major complications which were defined as radiographic failure, neurologic deterioration, and adverse events determined to be major complications by an independent Clinical Events Committee (CEC). In the TDR group, radiographic failure deemed to be a major complication was defined as: Spontaneous fusion of the treatment level with radiographic evidence of bridging bone across the treated disc space and less than 2° of angular motion from flexion to extension. In the ACDF group, radiographic failure deemed to be a major complication was defined as: Pseudoarthrosis at the treated level demonstrated by greater than or equal to 2° of angular motion on flexion to extension, or radiolucent lines at greater than 50% of the graft vertebral interfaces, or absence of bridging bone across the graft vertebral interfaces. This composite measure of success was used to determine overall success rates for both groups. Study surgeries were performed for the 245 patients in the ITT population and the 15 nonrandomized training cases that received the investigational device between April 2006 and March 2008. The study was conducted by 25 principal inves